Washington University has a long record of excellence in musculoskeletal research and clinical care. Historically the base for the research efforts have been individual laboratories in the Departments of Medicine, Orthopaedic Surgery and Pathology. In recent years, ad hoc collaborations have developed between these groups and non-musculoskeletal investigators in Departments of Anatomy & Neurobiology, Biomedical Engineering, Cell Biology, Developmental Biology, Genetics and Pediatrics, thereby significantly expanding our biological skill set and vision. However, we have lacked a central mechanism to leverage these new collaborations efficiently into new research discoveries. With this broad, diverse research base, we propose to create the Washington University Core Center for Musculoskeletal Biology and Medicine (CCMBM). The CCMBM Research Base has 48 members who have over 21 million dollars of annual research support (direct costs). Seventeen of the members have NIAMS funding (21 research grants). The primary goals of the Center are to enhance the productivity of established musculoskeletal scientists, to support young investigators in our field and to facilitate collaboration between established skeletal scientists and those bringing non-traditional questions and strategies to our discipline. The major programmatic focus of the CCMBM will be to support and expedite the creation and analysis of animal models of relevance to musculoskeletal biology and disease. Three Research Cores are proposed: Musculoskeletal Structure and Strength (Core B), In Situ Molecular Analysis (Core C), and Mouse Genetic Models (Core D). Our basic and translational research efforts will be directed toward an understanding of musculoskeletal biology at the molecular, cellular and tissue levels with the goal that such studies will directly impact our understanding of the pathophysiology of osteoporosis, osteoarthritis, muscular dystrophy, osteochondrodysplasias as well as regeneration of bone, cartilage, tendon and muscle. Through the Administrative Core (Core A), the CCMBM will sponsor enrichment activities to promote the exchange of information, ideas and reagents between CCMBM members, and to engage non-members who are doing meritorious research of interest to the CCMBM membership. We will also implement a Pilot & Feasibility Grant Program to provide funding support to young investigators in our field as well as to established, non-musculoskeletal investigators who propose to apply their outside expertise to a problem in musculoskeletal biology or medicine.